CML

Question 1

What are leukaemias?

Answer 1

A group of disorders characterized by the accumulation of malignant white cells in the bone marrow and blood

These abnormal cells cause symptoms due to bone marrow failure and infiltration of organs.

Question 2

What are the two main classifications of leukaemias?

Answer 2

• Acute
• Chronic

Acute leukaemias are further subdivided into myeloid and lymphoid, while chronic leukaemias are also subdivided into myeloid and lymphoid.

Question 3

What is Chronic Myeloid Leukaemia (CML)?

Answer 3

A clonal disorder of a pluripotent stem cell characterized by the presence of the Philadelphia (Ph) chromosome

CML accounts for 15-20% of adult leukaemia cases.

Question 4

What is the incidence of CML?

Answer 4

Approximately 1-2 cases per 100,000 per year, median age at diagnosis varies by region

In Nigeria, the median age is 37 years; in the US, it is 65-74 years; in Europe, it is 60-65 years.

Question 5

What genetic abnormality is associated with CML?

Answer 5

Translocation of part of the long arm of chromosome 22 to the long arm of chromosome 9, resulting in the Philadelphia chromosome

This involves the fusion of BCR and ABL1 genes leading to a fusion protein.

Question 6

What is the main feature of laboratory findings in CML?

Answer 6

Leucocytosis, which may reach levels greater than 200 × 10^9/L

A complete spectrum of myeloid cells is observed with characteristic basophils.

Question 7

What are common clinical features of CML?

Answer 7

• Fatigue
• Night sweats
• Weight loss
• Abdominal discomfort
• Early satiety
• Anorexia
• Breathlessness

Rarely, patients may experience visual disturbances and priapism.

Question 8

What are the phases of CML?

Answer 8

• Chronic Phase (CP)
• Accelerated Phase (AP)
• Blast Phase (BP)

Each phase has distinct characteristics and prognosis.

Question 9

What is the mainstay of treatment for CML in the chronic phase?

Answer 9

Tyrosine kinase inhibitors (TKIs)

Examples include Imatinib (first generation), Dasatinib, Bosutinib, Nilotinib (second generation), and Ponatinib (third generation).

Question 10

What is the monitoring process for TKI therapy response?

Answer 10

Response can be assessed with molecular tests or cytogenetic tests, recommended until a complete cytogenetic response and a Major molecular response are achieved

RT-PCR is used to determine BCR-ABL1 transcript levels.

Question 11

True or False: CML is more common in females than males.

Answer 11

False

CML is commoner in males than females.

Question 12

What are the types of response to TKI therapy?

Answer 12

• Major Cytogenetic Response (MCyR)
• Complete Cytogenetic Response (CCyR)
• Major Molecular Response (MMR)

These responses are critical for assessing treatment effectiveness.

Question 13

What is the significance of the Philadelphia chromosome in CML?

Answer 13

It is indicative of the presence of the BCR-ABL1 fusion gene, a hallmark of the disease

The Philadelphia chromosome is formed by a balanced translocation t(9;22)(q34;q11).

Question 14

Fill in the blank: CML is characterized by the _______ fusion gene.

Answer 14

BCR-ABL1

Question 15

What are the common laboratory findings in CML?

Answer 15

• Normochromic normocytic anaemia
• Increased or normal platelet count
• Hypercellular bone marrow with granulopoietic predominance

Serum uric acid is usually raised.

Question 16

What is the prognosis for patients with CML treated with TKIs?

Answer 16

Prognosis has improved significantly and depends on the phase at presentation and depth of response to therapy

Meeting treatment milestones strongly influences prognosis.

Question 17

What is a characteristic finding in the chronic phase of CML?

Answer 17

Leukocytosis with granulocytic predominance, basophilia, and blast count less than 10%

Bone marrow shows hyperplasia and a high myeloid-to-erythroid (M:E) ratio.